Thyroid Cancer Incidence Unchanged After RAIT Therapy

Medscape

12-05-2025

No increase in the incidence of new thyroid cancer cases among patients treated with radioactive iodine therapy (RAIT) for Graves' disease was found in a large retrospective study, adding to a body of research suggesting minimal cancer risk from this therapy.
Researchers at Ito Hospital, Tokyo, Japan, a leading center for thyroid conditions, analyzed the records of patients diagnosed with Graves' disease at their institution between April 1997 and December 2022.
Among 23,179 cases of Graves' disease treated with RAIT, 17 developed thyroid cancer. Sixteen were diagnosed with papillary thyroid carcinoma (PTC), of which 15 were microcarcinomas.
The team, led by Koichi Ito, MD, PhD, also compared incidence rates of thyroid cancer among patients treated with medication or surgery. No cases occurred in the surgery group and there was no significant difference in the incidence rates of the medication and RAIT groups.
'Furthermore, most thyroid cancers that developed after RAIT were micro-PTCs, with no evidence suggesting a poor prognosis in histological or genotypical terms,' Ito and colleagues wrote.
An autoimmune disorder causing excess thyroid hormone production, Graves' disease affects an estimated 3% of women and 0.5% of men globally. Although medication, the common initial treatment, often leads to remission, persistent cases may require surgery or RAIT.
The study's findings were published online in the Journal of Clinical Endocrinology and Metabolism .
Reassuring Results
Medscape Medical News spoke with several thyroid disease experts unaffiliated with the study. Although they noted that the limitation of relying on retrospective data from a single hospital, all said the study was well-conducted overall and aligns with other research downplaying the link between RAIT and thyroid cancer risk in Graves' disease.
'It's not necessarily completely new, but it is somewhat reassuring,' said David Toro-Tobon, MD, an endocrinologist and assistant professor of medicine at the Mayo Clinic in Rochester, Minnesota.
This study suggests that if there is a risk for thyroid cancer from RAIT in patients with Graves' disease, it is 'very, very low,' Toro-Tobon said, and not substantial enough to outweigh the potential benefits to patients receiving this treatment.
He added that many patients become apprehensive about RAIT as an option after checking with 'Dr. Google.' Physicians must then clarify that patients with Graves' disease typically require lower doses of radiation than those with thyroid cancer, for whom risks are higher due to cumulative exposure.
Toro-Tobon highlighted a key strength of the study: All patients underwent thyroid ultrasonography at initial visit, allowing preexisting cases of thyroid cancer to be excluded. This distinguishes it from prior studies that likely included such cases in their results.
'In the other studies, we don't know if they had some kind of indolent or slow-growing thyroid nodule or thyroid cancer [prior to the RAIT],' he said.
Christopher R. McHenry, MD, a surgeon and researcher at MetroHealth, Cleveland, emphasized that several factors guide treatment decisions for patients in whom Graves' disease isn't resolved after 18 months of drug therapy. Continuing with drug therapy is not an ideal option, he said, given the side effects of medications used, including agranulocytosis. Surgery is often preferred for patients with Graves' eye disease or large goiters that cause compression symptoms.
'The advantage of surgery is that patients get better immediately,' McHenry said. 'RAIT is usually preferable in patients without eye disease and without a significant goiter.'
He added that, in his experience, patients are more often concerned about RAIT's effect on their eyes than cancer risk.
'This is in part related to other studies that have come to the same conclusion as [Ito and colleagues' paper], that there is no significant association between radioactive iodine treatment and development of thyroid cancer.'
Decades of Research Into RAIT/Cancer Risk
RAIT has been used as a therapy for thyroid disease since the 1940s, and assessments of its long-term safety began as early as 1961 with the US Public Health Service's Cooperative Thyrotoxicosis Therapy Follow-Up Study (CTTFUS). This project followed approximately 35,000 patients with thyroid disease treated with RAIT, thyroidectomy, drugs, or various combinations of these treatments from 1946 to 1968.
In 1974, an initial report from the CTTFUS in the Journal of Clinical Endocrinology & Metabolism found no significant increase in thyroid cancer incidence or mortality among RAIT-treated patients. However, subsequent studies produced mixed results, raising doubts about a cancer link for the therapy.
To clarify the risk, Elaine Ron, PhD, of the National Cancer Institute, and colleagues conducted a mortality follow-up through 1990 of the original CTTFUS population. In a 1998 paper in JAMA , they concluded that although a few thyroid cancer deaths might be attributed to RAIT, the therapy appeared broadly safe.
Ito and colleagues referenced this long history in their April 2025 paper, acknowledging that mixed findings have persisted. Although their new data support RAIT's minimal risk for thyroid cancer, the study doesn't definitively resolve this longstanding question, said Michael Via, MD, an endocrinologist, professor of medicine and director of the Thyroid Center at Mount Sinai School of Medicine in New York City.
'I don't foresee that changing anytime soon, unfortunately,' Via said. 'The jury will be out for a while on this one.'
This leaves endocrinologists with a complex matter to explain to patients, many of whom are surprised to learn decades of medical research hasn't delivered a clear answer.
Physicians need to help patients understand where the state of science is on this issue and weigh their treatment options, which can include continued drug therapy or surgery.
'Some patients are comfortable with the uncertainty and very comfortable with RAIT,' Via said. 'Other patients are not or may need to know definitively. In some cases, even any small risk potential can drive anxiety,' and lead them to consider other options.
Ito and coauthors, Via, Toro-Tobon, and McHenry reported no relevant financial disclosures.